Weight loss is known to have adverse consequences for bone health, particularly in postmenopausal women. Some research has indicated that physical activity, particularly weight-bearing activity, may offset bone loss. Breast cancer survivors may be at particular risk for adverse bone health given the bone loss associated with several treatment regimens. There is limited research on the effects of weight loss and exercise on bone health in cancer survivors. Several studies have suggested that exercise may offset bone loss in breast cancer survivors, but these studies have not included a weight loss component. Given that energy restriction is a key component to most successful weight loss regimens, understanding the role it has on bone health in postmenopausal breast cancer survivors, who are at increased risk for bone loss, is an important safety consideration. The ENERGY trial (Exercise and Nutrition to Enhance Recovery and Good health for You) is a vanguard weight loss trial of n=800 overweight and obese women age 21 and older with stage IC-IIIA breast cancer across four sites in the US (RO1CA14879). Weight loss is achieved primarily through energy restriction with concurrent emphasis on aerobic exercise to complement weight loss and promote maintenance of weight loss. Thus, it provides an ideal setting to examine the associations between weight change and physical activity with bone loss in postmenopausal breast cancer survivors. Our primary hypothesis is that weight loss and physical activity will be correlated with bone loss and remodeling among overweight and obese postmenopausal breast cancer survivors. We will examine this through the collection of supplementary data in the postmenopausal women (expected to be 75% of the n=200) enrolled in the ENERGY trial at the St. Louis site (at Washington University School of Medicine). The goal of this study is to characterize bone loss and remodeling during the primary weight loss phase (from randomization to 12 months). Our proposal is innovative in that it will be the first study to prospectively assess the effects of intentional weight loss and physical activity during weight loss, independently and together, on bone health in overweight and obese postmenopausal breast cancer survivors. This is significant as there is great attention to the need for weight management in breast cancer survivors given the adverse effects of obesity on morbidity and mortality in this population. Results on bone density can directly inform clinical practice and recommendations for women after breast cancer. Specifically, our aims are to measure the correlation between weight change and physical activity and bone loss among overweight and obese postmenopausal breast cancer survivors enrolled in a randomized controlled weight loss trial and, secondarily, to characterize the interaction between weight change and physical activity as it relates to bone loss. PUBLIC HEALTH RELEVANCE: Using supplemental data collected among postmenopausal breast cancer survivors newly enrolled in a randomized weight loss trial, we will evaluate the association between weight loss and physical activity and bone health, specifically bone mineral density and serum bone turnover markers. We will also explore whether weight loss and physical activity interact to influence bone health.